PRODUCT MONOGRAPH XYLOCARD

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© The Aspen Group, 2017. All rights reserved

PRODUCT MONOGRAPH

XYLOCARD®

20 mg/mL

(lidocaine hydrochloride injection USP)

Antiarrhythmic

Aspen Pharmacare Canada Inc

111 Queen Street East, Suite 450,

Toronto, Ontario

M5C 1S2

Date of Revision:

August 15, 2017

Control No.: 206687

XYLOCARD® is a registered trademark of the AstraZeneca group of companies.

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PRODUCT MONOGRAPH

NAME OF DRUG

XYLOCARD®

20 mg/mL

(lidocaine hydrochloride injection USP)

THERAPEUTIC CLASSIFICATION

Antiarrhythmic

ACTIONS AND CLINICAL PHARMACOLOGY

Mechanism of Action

The mode of action of the antiarrhythmic effect of XYLOCARD (lidocaine hydrochloride)

appears to be similar to that of procaine, procainamide, and quinidine. Ventricular excitability

is depressed and the stimulation threshold of the ventricle is increased during diastole. The

sinoatrial node is, however, unaffected. In contrast to the latter three drugs, XYLOCARD in

therapeutic doses does not produce a significant decrease in arterial pressure or in cardiac

contractile force. In larger doses, XYLOCARD may produce circulatory depression, but the

magnitude of the change is less than that found with comparable doses of procainamide.

Neither drug appreciably affects the duration of the absolute refractory period.

Onset of Action

The onset of action following a single intravenous injection varies from 45 to 90 seconds.

Duration of action is 10 to 20 minutes.

INDICATIONS AND CLINICAL USE

The intravenous administration of XYLOCARD (lidocaine hydrochloride) is indicated in the

treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or

catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or

other cardiac diseases.

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CONTRAINDICATIONS

XYLOCARD (lidocaine hydrochloride) is contraindicated in patients with:

1. Known hypersensitivity to local anesthetics of the amide type, such as prilocaine,

mepivacaine or bupivacaine, or to other components of the solution;

2. Adams-Stokes syndrome, or severe degrees of sinoatrial, atrioventricular or

intraventricular block.

The safety of XYLOCARD in the treatment of arrhythmias in children has not been

established.

WARNINGS

Constant ECG monitoring is essential for the proper administration of XYLOCARD

(lidocaine hydrochloride) intravenously. Signs of excessive depression of cardiac

conductivity, such as prolongation of PR interval and QRS complex, and the appearance of

aggravation of arrhythmias, should be followed by prompt cessation of the intravenous

infusion.

It is mandatory to have emergency resuscitative equipment and drugs immediately available to

manage possible adverse reactions involving the cardiovascular, respiratory, or central

nervous systems.

In emergency situations, when a ventricular rhythm disorder is suspected, and ECG equipment

is not available, a single dose may be administered when the physician in attendance has

determined that the potential benefits outweigh the possible risks. If possible, emergency

resuscitative equipment and drugs should be available.

PRECAUTIONS

XYLOCARD (lidocaine hydrochloride) should be used with caution in patients with

bradycardia, severe digitalis intoxication, first or second degree heart block in the absence of a

pacemaker, or hypokalaemia (see CONTRAINDICATIONS and WARNINGS).

In unconscious patients circulatory collapse should be watched for, since CNS effects may not

be apparent as an initial manifestation of toxicity.

Caution should be observed in patients with cardiac decompensation and hypotension or

posterior diaphragmal infarction with a tendency towards development of heart block.

Intravenous administration of XYLOCARD is sometimes accompanied by a hypotensive

response, and, in overdosage, this may be precipitous. For this reason the intravenous dose

should not exceed 100 mg in a single injection, and no more than 200-300 mg in a one hour

period (see DOSAGE and ADMINISTRATION).

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When high doses are used and the patient’s myocardial function is impaired, combination with

other drugs which reduce the excitability of cardiac muscle requires caution.

Repeated doses of XYLOCARD may cause significant increases in blood levels with each

repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to

elevated blood levels varies with the status of the patient. Debilitated, elderly patients and

acutely ill patients should be given reduced doses commensurate with their age and physical

condition. XYLOCARD should also be used with caution in patients with epilepsy, impaired

cardiac conduction, bradycardia, impaired hepatic function or renal function and in severe

shock.

Use in the Elderly

A reduction in dosage may be necessary for elderly patients, particularly those with

compromised cardiovascular and/or hepatic function and/or prolonged infusion. Elderly

patients should be given reduced doses corresponding to their age and physical status.

Impaired Renal Function

Caution should be employed in the repeated use of XYLOCARD in patients with severe renal

disease, since possible accumulation of lidocaine or its metabolites may lead to toxic

phenomena.

Impaired Hepatic Function

Caution should be employed in the repeated use of XYLOCARD in patients with severe liver

disease, since possible accumulation of lidocaine or its metabolites may lead to toxic

phenomena.

Use in Pregnancy

It is reasonable to assume that lidocaine has been used, mainly as a local anesthetic, by a large

number of pregnant women and women of child-bearing age. No specific disturbances to the

reproductive process have so far been reported, e.g., no increased incidence of malformations.

However, care should be taken during early pregnancy when maximum organogenesis takes

place.

There are no adequate and well-controlled studies with intravenous administration of lidocaine

in pregnant women.

Use in Nursing Mothers

Lidocaine is excreted in the breast milk, but in such small quantities that there is generally no

risk of affecting the infant at therapeutic dose levels.

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Use in Neonates

Through their lower enzyme capacity, very rarely, neonates are at risk of

methaemoglobinaemia. Methaemoglobinaemia can become clinically overt (cyanosis), and

treatment with methylene blue may be considered necessary.

Use in Patients with Acute Porphyria

Theoretical evidence suggests that lidocaine may have porphyrogenic properties. The clinical

significance of this is unknown. Caution should be exercised if intravenous lidocaine

(XYLOCARD) is administered to patients with acute porphyria.

Drug Interactions

Lidocaine is mainly metabolized in the liver by CYP1A2 and CYP3A4 to its two major

metabolites, monoethylglycinexylidine (MEGX) and glycinexylidine (GX), both of which are

pharmacologically active. Lidocaine has a high hepatic extraction ratio. Only a small fraction

(3%) of lidocaine is excreted unchanged in the urine. The hepatic clearance of lidocaine is

expected to depend largely on blood flow.

Since the affinity of lidocaine to CYP1A2 and CYP3A4 is very low compared to therapeutic

plasma concentrations, it is less likely that the metabolism of substrates for these enzymes will

be inhibited when coadministered with lidocaine. However, there is a potential for influence

of other drugs on the plasma levels/effect of lidocaine, e.g. strong inhibitors or inducers of

CYP1A2 and/or CYP3A4 and drugs that affect liver blood flow (see Table 1).

Table 1 Established or Potential Drug-Drug Interactions

Name Reference Effect Clinical comment

Strong inhibitors of

CYP1A2

(fluvoxamine)

CT Coadministration of

fluvoxamine, reduced [41%]

the elimination of lidocaine in

healthy subjects.

Given concomitantly with

lidocaine, strong inhibitors of

CYP1A2 can cause a

metabolic interaction leading

to increased lidocaine plasma

concentrations.

Therefore,

coadministration of

lidocaine should be

avoided in patients

treated with strong

inhibitors of

CYP1A2, such as

fluvoxamine.

CYP1A2 inducers

(Phenytoin)

T During concomitant

administration of lidocaine

and CYP1A2 inducers,

plasma levels/effect of

Higher dose of

lidocaine may be

required.

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lidocaine may decrease.

Strong inhibitors of

CYP3A4

(erythromycin,

itraconazole)

CT Erythromycin and

itraconazole have each been

shown to have a modest or no

effect on the

pharmacokinetics of

intravenous lidocaine (0-18%

decreased elimination with

erythromycin but no effect

with itraconazole).

No dose adjustment

seems required.

CYP3A4 inducers

(carbamazepine,

phenobarbital,

phenytoin,

primidone)

CT Concomitant administration

with carbamazepine,

phenobarbital, phenytoin, and

primidone, may slightly

decrease plasma levels of

lidocaine (<10%).

No dose adjustment

seems required.

Beta-blockers

(propranolol,

metoprolol, nadolol)

CT Propranolol, metoprolol, and

nadolol have been reported to

reduce intravenous lidocaine

clearance, probably through

effects on hepatic blood flow

and/or metabolism, and may

increase the plasma

concentration of lidocaine by

about 30%, less with

metoprolol.

Therefore,

concomitant

administration of

beta-blockers with

lidocaine should be

avoided. If not

possible, close

monitoring and dose

adjustment may be

required.

Cimetidine CT Cimetidine has an unspecific

inhibitory effect on CYP

(including CYP1A2 and CYP

3A4) mediated metabolism

and reduces hepatic blood

flow.

Clinical experiments showed

that the concomitant

administration of cimetidine

reduces the systemic

clearance of lidocaine and

increases lidocaine serum

Therefore,

concomitant

administration with

lidocaine should be

avoided. If not

possible, close

monitoring and dose

adjustment of

lidocaine and/or

cimetidine may be

required.

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concentration by as much as

50%. Thus, therapeutic

serum levels of lidocaine may

rise to toxic levels when

cimetidine is used

concomitantly. Ranitidine

has not displayed this effect.

Amiodarone CT, C Like cimetidine, amiodarone

has an unspecific inhibitory

effect on CYP mediated

metabolism. Concomitant

administration has resulted in

increased plasma levels of

lidocaine and may result in

toxic effects.

Therefore,

concomitant

administration with

lidocaine should be

avoided. If not

possible, close

monitoring and dose

adjustment of

lidocaine and/or

amiodarone may be

required.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies of lidocaine in animals to evaluate the carcinogenic and mutagenic potential or the

effect on fertility have not been conducted.

ADVERSE REACTIONS

Adverse experiences following the administration of lidocaine are similar in nature to those

observed with other amide type agents. These adverse experiences are, in general, dose-

related and may result from high plasma levels caused by excessive dosage or rapid

absorption, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the

part of the patient.

Common adverse reactions are those from the central and peripheral nervous system. They

occur in 5-10% of the patients and are mostly dose-related. The following definitions of

frequencies are used: Very common ( ≥ 10%), common (1 – 9.9%), uncommon (0.1 – 0.9%),

rare (0.01 – 0.09%) and very rare (< 0.01%).

Systemic reactions of the following types have been reported:

Central Nervous System

CNS manifestations are excitatory and/or depressant. Common adverse reactions are

circumoral paresthesia, dizziness and drowsiness. Rare adverse reactions would include

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persistent dizziness, lightheadedness, nervousness, apprehension, euphoria, confusion,

hyperacusis, tinnitus, blurred vision, vomiting, sensations of heat, cold or numbness,

twitching, tremors, convulsions, unconsciousness, apnea, respiratory depression and arrest.

The excitatory manifestations may be very brief or may not occur at all, in which case the first

manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory

arrest.

Drowsiness following the administration of lidocaine is usually an early sign of a high

lidocaine plasma level and may occur as a consequence of rapid absorption.

Cardiovascular System

Rare cardiovascular manifestations are usually depressant and are characterized by

bradycardia, hypotension, asystole and cardiovascular collapse which may lead to cardiac

arrest. Arrhythmias, including ventricular tachycardia/ventricular fibrillation have also been

reported.

Hematologic System

Very rarely, neonatal methaemoglobinaemia can occur (see Precautions).

Immune System

Allergic reactions are characterized by cutaneous lesions, urticaria, edema, or in the most

severe and very rare instances, hypersensitivity including anaphylactic shock. Allergic

reactions of the amide type are rare and may occur as a result of sensitivity either to the drug

itself, or to other components of the formulation.

Idiosyncratic reactions have been reported at low doses in some patients. Cross-sensitivity

between XYLOCARD and procainamide or XYLOCARD and quinidine have not been

reported.

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Symptoms of idiosyncratic reactions are described under ADVERSE REACTIONS.

Symptoms

Lidocaine toxicity may appear at serum concentrations greater than 8 mg/L. The most serious

effects of lidocaine intoxication are on the central nervous system and cardiovascular system

and overdosage can result in dizziness, delirium, severe hypotension, conduction defects,

bradycardia, asystole, arrhythmias, including ventricular tachycardia/fibrillation,

cardiovascular collapse which may lead to cardiac arrest, apnea, seizures, coma, respiratory

arrest and death.

Central nervous system toxicity is a graded response, with symptoms and signs of escalating

severity. The first symptoms are circumoral paresthesia, numbness of the tongue,

lightheadedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors are more

serious and precede the onset of generalized convulsions. Unconsciousness and grand mal

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convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and

hypercarbia occur rapidly following convulsions due to the increased muscular activity,

together with the interference with normal respiration. In severe cases apnea may occur.

Acidosis increases the toxic effects.

Recovery is due to redistribution and metabolism of the drug. Recovery may be rapid unless

large amounts of the drug have been administered.

Cardiovascular effects may be seen in cases with high systemic concentrations. Severe

hypotension, bradycardia, arrhythmia and cardiovascular collapse may be the result in such

cases.

Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous

system, unless the patient is receiving a general anesthetic or is heavily sedated with drugs

such as a benzodiazepine or barbiturate.

Treatment

The first consideration is prevention, best accomplished by careful and constant monitoring of

cardiovascular and respiratory vital signs and the patient's state of consciousness. At the first

sign of change, oxygen should be administered.

The first step in the management of convulsions consists of immediate attention to the

maintenance of a patent airway and assisted or controlled ventilation with oxygen and a

delivery system capable of permitting immediate positive airway pressure by mask.

Immediately after the institution of these ventilatory measures, the adequacy of the circulation

should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress

the circulation when administered intravenously.

An anticonvulsant should be given i.v. if the convulsions do not stop spontaneously in 15-20

seconds. Thiopental 100-150 mg i.v. will abort the convulsions rapidly. Alternatively,

diazepam 5-10 mg i.v. may be used, although its action is slower. Succinylcholine will stop

the muscle convulsions rapidly, but will require tracheal intubation and controlled ventilation,

and should only be used by those familiar with these procedures.

Hypotension may be counteracted by giving sympathicomimetic drugs (e.g., adrenaline).

Adrenergic agents of both α-adrenoceptor stimulating (e.g., metaraminol) and β-adrenoceptor

stimulating type (e.g., isoprenaline) are generally effective. The bradycardia may be treated

with parasympatholytic agents (e.g., atropine).

Should circulatory arrest occur, immediate cardiopulmonary resuscitation should be instituted.

Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis

are of vital importance, since hypoxia and acidosis will increase the systemic toxicity of local

anesthetics. Epinephrine (0.1-0.2 mg as intravenous or intracardial injections) should be given

as soon as possible and repeated, if necessary.

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DOSAGE AND ADMINISTRATION

Single Intravenous Injection

The usual dose is 50 to 100 mg XYLOCARD (lidocaine hydrochloride) administered under

ECG and blood pressure monitoring. This dose may be administered at the rate of

approximately 25 to 50 mg/min. Sufficient time should be allowed to enable a slow

circulation to carry the drug to the site of action. If the initial injection of 50 to 100 mg does

not produce a desired response, a second dose may be repeated after 10 minutes. NO MORE

THAN 200 TO 300 MG OF XYLOCARD SHOULD BE ADMINISTERED DURING A

ONE HOUR PERIOD.

Continuous Intravenous Infusion

Following intravenous injection, XYLOCARD may be administered by intravenous infusion

at a rate of 1-2 mg/min (approximately 15-30 µg/kg/min in the average 70 kg patient) in those

patients in whom the arrhythmia tends to recur, and who are incapable of receiving oral

antiarrhythmic therapy.

Intravenous infusions of XYLOCARD must be administered under constant ECG and blood

pressure monitoring and with meticulous regulation of infusion rate, in order to avoid

potential overdosage and toxicity.

Intravenous infusions should be terminated as soon as the patient's basic cardiac rhythm

appears to be stable or at the earliest signs of toxicity. It should rarely be necessary to

continue intravenous infusion beyond 24 hours. As soon as possible, and when indicated,

patients should be changed to an oral antiarrhythmic agent for maintenance therapy.

Solution for intravenous infusion may be prepared by the addition of one gram of

XYLOCARD (i.e., contents of ten 5 mL ampoules) to one litre of an appropriate infusion

solution. Approximately a 0.1% solution will result from this procedure; that is, each mL will

contain approximately 1 mg of XYLOCARD.

In those cases in which fluid restriction is medically desirable a more concentrated solution

may be prepared by adding one gram of XYLOCARD (i.e., contents of ten 5 mL ampoules) to

500 mL of diluent. Approximately a 0.2% solution will result from this procedure; that is,

each mL will contain approximately 2 mg of XYLOCARD.

Solutions should be prepared using aseptic technique. As with all intravenous admixtures,

dilution should be made just prior to administration. Prepared solutions should be used within

12 hours.

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PHARMACEUTICAL INFORMATION

Drug Substance

Proper name: Lidocaine hydrochloride

Chemical Name: 2-(Diethylamino)-2',6'-acetoxylidide monohydro-chloride monohydrate

Structural Formula:

Molecular Formula: C14H22N2OH2O

Molecular Weight: 288.82

Description: Lidocaine hydrochloride is a white, odourless, crystalline powder which has a

slightly bitter taste. It is very soluble in water and in alcohol, soluble in

chloroform and insoluble in ether.

Composition/mL

XYLOCARD

100 mg

Active:

Lidocaine

hydrochloride

20 mg

Non-medicinal:

Sodium chloride

for (isotonicity)

Water for

injection

6 mg

Sodium hydroxide and/or hydrochloric acid to adjust pH to 5.0-7.0.

Stability and Storage Recommendations

Store at room temperature (15-30°C).

XYLOCARD solutions are preservative free and are for single use. Discard unused portion.

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AVAILABILITY OF DOSAGE FORMS

Single Intravenous Injection

XYLOCARD 100 mg is available in a 5 mL glass ampoule (contains 20 mg/mL, a 2%

solution).

Continuous Intravenous Infusion

5% dextrose in water is the preferred diluent.

See DOSAGE and ADMINISTRATION section for instructions regarding preparation of

solutions for continuous intravenous infusion.

PHARMACOLOGY

Lidocaine hydrochloride is a well known anesthetic agent which has been used for many years

for regional and topical anesthesia. However, it has been demonstrated to exert an

antiarrhythmic effect by increasing the electrical stimulation threshold of the ventricle during

diastole.

In decerebrated, vagotomized cats with stellate ganglia destroyed, lidocaine hydrochloride

intravenous suppressed cardiac arrhythmias induced by faradic stimulation, barium chloride

and epinephrine. The minimal effective dose was 0.5 mg per kg. This was 4 and 5 times less

than the minimal doses of procaine and procainamide respectively.

In anesthetized open-chest dogs, lidocaine hydrochloride 5 mg per kg intravenously reduced

the duration of methacholine-induced auricular arrhythmias by 55.5%. The effect of quinidine

sulphate at the same dose was a reduction 46.5%. Ventricular arrhythmias induced by

coronary ligation were controlled by total intravenous doses of 50 mg/kg. Convulsions and

vomiting were produced and death occurred in 1 of 6 dogs at 75.5 mg/kg. In the same

preparation, interruption of the arrhythmia was obtained by an injection of 15 mg/kg directly

into the ventricle. In normothermic or hypothermic dogs the same effect was obtained in

ventricular fibrillation induced by mechanical stimulation.

In anesthetized dogs, intravenous infusions of 40-80 mg converted digitalis-induced

ventricular arrhythmia to sinus rhythm. Also, acetylstrophanthidin-induced ventricular

tachycardia was suppressed at a minimal effective dose of lidocaine hydrochloride of 1 mg/kg

intravenously. Digitalis-induced ventricular tachycardia, which failed to respond to electro-

shock was converted to normal sinus rhythm by intravenous injection of lidocaine

hydrochloride 100 mg and ventricular tachycardia, induced by ouabain, was converted to

supraventricular tachycardia by intravenous injection of 1-2 mg/kg.

In unanesthetized dogs with ventricular arrhythmia induced by coronary occlusion,

intravenous injections of 5-10 mg/kg suppressed the arrhythmia. This effect could be

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maintained by intravenous infusion with calculated lidocaine hydrochloride blood levels of

1-3 µg/mL.

Other effects in anesthetized intact dogs were depression of myocardial contractile force, heart

rate and femoral arterial pressure with lidocaine hydrochloride 0.5 to 6 mg/kg intravenously.

At 2.0 mg/kg intra-arterially the same effects were obtained but there was less diminution of

contractile force. In both anesthetized and conscious dogs, lidocaine hydrochloride in rapid

intravenous injection of 2, 4 and 8 mg/kg caused transient decrease of systolic arterial

pressure, venous pressure, cardiac output, mean ejection rate, rate of development of arterial

pressure, stroke work and calculated peripheral resistance. Heart rate was slightly increased.

Effects were greatest at 8 mg/kg and were more pronounced and of longer duration in

anesthetized dogs. There was return to basal levels in 3-5 minutes.

Absorption, Distribution and Excretion

In rats which received 14

C-labelled lidocaine hydrochloride by intravenous injection, rapid

uptake by all tissues was noted. Tissue distribution studies in monkeys have indicated: high

affinity for lung, spleen, kidney, stomach and adipose tissue; moderate affinity for brain and

most gastrointestinal organs; and low affinity for musculoskeletal tissue and skin. Similar

distribution has been observed in the dog.

Studies on plasma binding in monkey and man have indicated approximately 60% plasma

binding within the plasma concentration range usually seen in clinical use. However, plasma

binding was markedly reduced at concentrations of lidocaine hydrochloride exceeding

10 μg/mL, presumably due to saturation of the binding sites.

Studies in rabbit and rat have demonstrated that the liver is the principal site of metabolism.

In man, hepatic clearance studies have shown that approximately 70% of the lidocaine

hydrochloride passing through the liver was extracted. Microsomal enzyme systems are

primarily responsible for hepatic metabolism. The major degradative pathway appears to be

by conversion to monoethylglycinexylidide, followed by hydrolysis to 2,6,-xylidine; further

conversion to 4-hydroxy-2,6-xylidine appears to occur in man.

Up to 10% of administered lidocaine hydrochloride may be excreted in the urine as unchanged

drug. Although biliary secretion and intestinal absorption of lidocaine hydrochloride

metabolites have been reported in rats, there is no evidence of biliary secretion in man.

The pharmacokinetics of lidocaine hydrochloride has been studied in normal subjects and in

patients.

Following a single intravenous injection, or termination of a continuous intravenous infusion,

declining plasma concentration follows a biphasic curve. Plasma half-lives of 8 to 15 minutes

have been reported for the initial phase. Various studies have reported the mean half-life at

the terminal phase to be in the range 1.2 to 1.9 hours. The minimum effective antiarrhythmic

plasma concentration of lidocaine hydrochloride has been reported to be in the range of 1.0 to

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1.2 μg/mL; concentrations higher than 5-6 μg/mL are associated with an increased risk of

toxicity.

TOXICOLOGY

Acute Toxicity

SPECIES SEX ROUTE LD50(mg/kg)

mice F i.v. 17.9

mice F i.p. 164

mice F i.m. 200

mice M i.m. 154

rat F i.v. 19.7

rat M i.v. 21.4

dog M & F i.m. 100

guinea pig F i.m. 73

guinea pig M i.m. 67

rabbit M i.m. 450

Acute intravenous studies were performed in rabbits which received six serial injections of 1,

2, 3, 4 or 5 mg/kg at 15 minute intervals. At the 2 mg/kg dose level, slight depression was

seen, beginning with the third injection. At 3 mg/kg there was depression and rigid extension

of limbs after the last 5 injections. At 5 mg/kg there was severe depression and rigid limb

extension after each injection; loss of righting reflex and convulsions began with the second

injection and there was gasping for breath after each of the last injections.

Dogs were given intravenous incremental doses at 30 minute intervals until death occurred.

Doses of 0.1 to 3.0 mg/kg were tolerated with minimal CNS or cardiovascular effects.

Convulsions, mydriasis, salivation, urination and defecation were observed after 10 mg/kg.

Respiratory arrest and death occurred in one dog after 30 mg/kg; cardiovascular collapse,

respiratory arrest and death occurred in remaining animals after 100 mg/kg. Mean arterial

blood pressure and heart rate increased briefly, beginning at 3.0 mg/kg, and decreased after

100 mg/kg. Myocardial conduction time was not significantly changed prior to 100 mg/kg

administration.

Acute local responses were studied in rats and rabbits following single intramuscular

injections of 2%, 4%, 6%, 8% and 10% solutions of lidocaine hydrochloride. Microscopic

examination revealed inflammatory changes with all solutions. In general, reactions produced

by 2% solutions were least, although lesions seen with all other concentrations were of similar

degree.

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In rabbits sacrificed seven days after intramuscular administration, there was evidence of

marked muscle fiber regeneration; after 30 days there was virtually complete resolution of

inflammatory changes at the site of injection.

Subacute Toxicity

In one study, dogs received daily intravenous injections according to the following schedule:

0.1 mg/kg for 7 days, 0.3 mg/kg for 7 days, 1 mg/kg for 7 days and 3 mg/kg for 21 days. Mild

transient convulsions were seen in one dog at the high dose level. No other signs of toxicity

were observed. Gross and microscopic examination at autopsy did not reveal any drug related

effects.

In a second study, dogs received daily intravenous injections of 2.5, 5 or 10 mg/kg for 28

days. No overt symptoms were observed at the low dose level. At the 5 mg/kg level there

was transient sedation, ataxia, head tremor, prostration and emesis. At the 10 mg/kg level

there were severe tremors, muscular weakness, ataxia, prostration and convulsions, although

animals recovered within 5-10 minutes. No ECG or hemochemistry changes were seen. No

evidence of drug-related pathology was seen at autopsy. Injection sites showed inflammatory

changes in drug and saline-treated animals.

In rats which received daily intravenous doses of 1.5, 4.5 or 15.0 mg/kg for 14 days, overt

effects were observed only at the 15.0 mg/kg level, at which convulsions and death occurred.

Increased blood glucose levels were seen in male rats at all dose levels. At autopsy, no

changes were attributed to drug treatment. Mild inflammatory changes were seen at injection

sites.

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New Eng J Med 1967;277:1216.

Graham CF, Turner WM, Jones, JK.

Lidocaine-Propranolol Interactions. New Eng J Med 1981;304(21):1301.

Grossman J, Lubow LA, Frieden J, Rubin IL.

Lidocaine in cardiac arrhythmias. Arch Int Med 1968;121:396.

Ha et al.

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539.

Harris AS, Guerra CA, Liptak RA, Brigham, JC.

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Lignocaine in the management of arrhythmias after acute myocardial infarction.

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IMPORTANT: PLEASE READ


PART III: CONSUMER INFORMATION

XYLOCARD®

lidocaine hydrochloride injection

Read this carefully before you start taking

XYLOCARD and each time you get a refill. This

leaflet is a summary and will not tell you

everything about XYLOCARD. Talk to your

doctor, nurse, or pharmacist about your medical

condition and treatment and ask if there is any

new information about XYLOCARD.

ABOUT THIS MEDICATION

What the medication is used for:

XYLOCARD is used to treat abnormal heart

rhythms that may occur during heart surgery or

other procedures, heart attacks or due to other heart

conditions.

What it does:

XYLOCARD belongs to a class of drugs called

antiarrhythmic drugs. It works by reducing the

excitability of the heart which helps return the

heartbeat to normal.

When it should not be used:

Do not use XYLOCARD if you:

are allergic or sensitive to lidocaine

hydrochloride, to any of the nonmedicinal

ingredients in XYLOCARD or other local

anaesthetics (e.g. prilocaine, mepivacaine

or bupivacaine).

have Adams-Stokes syndrome, or severe

degrees of sinoatrial, atrioventricular or

intraventricular block.

What the medicinal ingredient is:

lidocaine hydrochloride

What the nonmedicinal ingredients are:

Sodium chloride, sodium hydroxide (and/or

hydrochloric acid) and water for injection

What dosage forms it comes in:

Liquid: 20 mg/mL

WARNINGS AND PRECAUTIONS

BEFORE you use XYLOCARD talk to your

doctor, nurse or pharmacist if you:

have a slow heartbeat.

have low levels of potassium in your

blood.

have epilepsy.

have low blood pressure.

have problems with your heart, liver or

kidneys.

have been diagnosed with acute porphyria.

are experiencing severe shock.

are pregnant or plan to become pregnant.

are breastfeeding or planning to breastfeed.

INTERACTIONS WITH THIS MEDICATION

As with most medicines, interactions with other

drugs are possible. Tell your doctor, nurse, or

pharmacist about all the medicines you take,

including drugs prescribed by other doctors,

vitamins, minerals, natural supplements, or

alternative medicines.

The following may interact with XYLOCARD:

Antiarrhythmic drugs used to treat heart

problems such as; mexiletine,

amiodaraone.

Other anesthetics such as; lidocaine.

Cimetidine used for stomach problems.

Fluvoxamine used to treat depression.

Drugs used to treat migraines.

Antipsychotic drugs.

Beta-blockers, used to treat heart

problems, such as; metoprolol, nadolol,

propranolol.

Drugs used to treat epilepsy and seizures

such as; carbamazepine, phenobarbital,

phenytoin, primidone.

PROPER USE OF THIS MEDICATION

Usual dose:

XYLOCARD must be administered by a doctor.

The doctor will decide on the dose you will be

given based on your individual needs.

Overdose:

Serious side effects can occur if you are given too

much XYLOCARD. Early signs that too much

XYLOCARD has been given include:

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numbness of the lips and around the

mouth,

lightheadedness or dizziness,

blurred vision,

hearing problems and/or ringing in the

ears.

In the event of a serious overdose, trembling,

seizures or unconsciousness may occur.

If you think you have been given too much

XYLOCARD, contact your doctor, nurse, hospital

emergency department or regional Poison Control

Centre immediately, even if there are no symptoms.

SIDE EFFECTS AND WHAT TO DO ABOUT

THEM

Side effects may include:

nausea, vomiting

dizziness, lightheadedness

drowsiness

sensations of heat, cold or numbness

sensitivity to sounds, ringing in the ears

If any of these affects you severely, tell your

doctor, nurse or pharmacist.

SERIOUS SIDE EFFECTS, HOW OFTEN THEY

HAPPEN AND WHAT TO DO ABOUT THEM

Symptom / effect Talk with

your doctor,

nurse or

pharmacist

Stop

taking

drug and

seek

immediate

medical

help

Only

if

severe

In

all

cases

Common

Abnormal

sensations: pins

and needles,

numbness

around the

mouth and/or of

the tongue

√

Slow or

irregular

heartbeat

√




your doctor,

nurse or

pharmacist

Stop

taking

drug and

seek

immediate

medical

help

Only

if

severe

In

all

cases

High blood

pressure: headache,

dizziness,

shortness of

breath, vision

problems

√

Low blood

pressure:

dizziness,

fainting,

lightheadedness.

May occur

when you go

from lying or

sitting to

standing up.

√

Rare

Prolonged

dizziness

√

Heart attack: severe crushing

chest pain,

irregular

heartbeat,

shortness of

breath

√

Allergic

reaction: rash,

hives, swelling

of the face, lips,

tongue or throat,

difficulty

swallowing or

breathing

√

Nerve injury: paralysis or

tingling of the

arms and legs

√

Vision

problems: blurred vision

√

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your doctor,

nurse or

pharmacist

Stop

taking

drug and

seek

immediate

medical

help

Only

if

severe

In

all

cases

Nervous

system

disorders: nervousness,

apprehension,

euphoria,

confusion,

twitching,

tremors,

convulsions,

unconsciousness

√

Respiratory

arrest: severe

trouble

breathing,

unconsciousness

√

This is not a complete list of side effects. For any

unexpected effects while taking XYLOCARD

contact your doctor, nurse or pharmacist.

HOW TO STORE IT

Store at room temperature (15-30ºC).

Keep out of reach and sight of children.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions

associated with the use of health products to the

Canada Vigilance Program by one of the following 3

ways:

---------------------------------------------------------------------

Report online at

www.healthcanada.gc.ca/medeffect

Call toll-free at 1-866-234-2345

Complete a Canada Vigilance Reporting

Form and:

- Fax toll-free to 1-866-678-6789, or

- Mail to: Canada Vigilance Program

Health Canada

Postal Locator 0701D

Ottawa, Ontario

K1A 0K9

Postage paid labels, Canada Vigilance Reporting

Form and the adverse reaction reporting guidelines

are available on the MedEffect™ Canada Web site at

www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the

management of side effects, contact your health

professional. The Canada Vigilance Program does not

provide medical advice.

MORE INFORMATION

NOTE: This CONSUMER INFORMATION leaflet

provides you with the most current information at

the time of printing.

The most current information, the Consumer

Information leaflet plus the full Product

Monograph, prepared for health professionals can

be found at: www.aspenpharma.ca, or by contacting

the sponsor, Aspen Pharmacare Canada Inc. at: 1-

844-330-1213.

This leaflet was prepared by

Aspen Pharmacare Canada Inc, 111 Queen Street

East, Suite 450, Toronto, Ontario, M5C 1S2

XYLOCARD® is a registered trademark of the

AstraZeneca group of companies.

Last revised: August 15, 2017.

http://www.healthcanada.gc.ca/medeffect

PRODUCT MONOGRAPH XYLOCARD

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